Burkholderia mallei
Classification
Domain: Bacteria
Phylum: Pseudomonadota
Class: Betaproteobacteria
Order: Burkholderiales
family: Burkholderiaceae
genus: Burkholderia
Species
Burkholderia mallei
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NCBI: Taxonomy |
Genus species
Description and Significance
Burkholderia mallei is a Gram-negative, bipolar, aerobic, non-motile bacterium that does not produce spores. It is a small, rod-shaped bacterium that develops slowly in most culture conditions and is a facultative intracellular pathogen. This host-adapted bacterium may survive in the environment for a brief time and is responsible for glanders, a zoonotic illness that mostly affects horse populations and other animals but is rare in humans.[1] B. mallei is closely related to B. pseudomallei, and genetic studies indicate that it arose as a subspecies of B. pseudomallei via selective reduction and deletions from the B. pseudomallei genome, most likely adapting to an intracellular lifestyle within animal hosts.[2] B. mallei, unlike B. pseudomallei and other members of the genus, is non-motile and has a coccobacillary shape, measuring 1.5-3.0 μm in length, 0.5-1.0 μm in diameter, and rounded ends.
The Centers for Disease Control and Prevention (CDC) classifies B. mallei as a category B select agent due to its high infectiousness, potential for biological warfare and bioterrorism, and hazard to public health and agriculture.[3] The development of improved diagnostic tools, vaccines, and therapeutic strategies for this pathogen is important. B. mallei was one of the earliest biological warfare agents utilized in the nineteenth century, particularly during World War I, when German agents purposely infected horses and livestock in the United States, Spain, Norway, and other nations via inoculation and feed contamination.[4] While B. mallei cannot survive outside of its host, thus restricting its utility as a bioweapon, other countries, such as Japan and Russia, have investigated it as a potential biological weapon. Despite its inability to survive outside of a host, B. mallei's high infectivity and potential for serious harm to human and animal populations make it a troubling virus that necessitates continued research and preparedness measures.[5]
Genome Structure
Burkholderia mallei's genome exhibits distinctive features that differentiate it from other members of the Burkholderia genus. Unlike its closely related counterpart, B. pseudomallei which has a larger genome (around 7.3 Mb) size, B. mallei possesses a smaller genome with unique characteristics (around 3.5 mb). While B. pseudomallei has a larger genome size, Burkholderia mallei's genome is relatively smalle. Which can reflect selective reduction and deletions from the B. pseudomallei genome during its evolution into a specialized and unique pathogen. B. mallei's genome provides insights into its phylogenetic relationship with other members of the Burkholderias genus and related organisms. Multilocus sequence typing has classified Burkholderia mallei as a subspecies of B. pseudomallei due to clone reduction. Indicating a close evolutionary relationship. However, genomic analysis reveals distinct genetic differences between the two species, reflecting their differences in ecological niches and lifestyles as pathogens. Overall the genome is structured as being made up of 2 circular chromosomes each with their own designated roles. Chromosome one harbors essential genes for basic cellular functions while chromosome 2 contains genes associated with adaptation, virulence and pathogenicity. Understanding th genome structure of B. Mallei is crucial for dissecting its pathogenic mechanisms, evolutionary history and adaptation to its host environment. This is possible from comparative genomic analysis which provides strategies for diagnosis, treatment and prevention of infections caused by the pathogens.
Cell Structure, Metabolism and Life Cycle
B. mallei exhibits distinctive cellular features that contribute to its pathogenicity and survival in various host environments. Burkholderia mallei cells are typically coccobacilli, measuring approximately 1.5–3.0 μm in length and 0.5–1.0 μm in diameter, with rounded ends. Unlike its motile counterpart B. pseudomallei, Burkholderia mallei is nonmotile. As discussed earlier the cell wall of Burkholderia mallei is Gram-negative, characterized by an outer membrane containing lipopolysaccharides (LPS) that contribute larg;y to its pathogenic properties and interaction with host cells. Burkholderia mallei usually produces a thick capsule composed of polysaccharides which serves as a virulence factor protecting the bacterium from host immune defenses and its survival in the host environment.
Burkholderia mallei uses a wide diverse range of metabolic pathways to obtain energy and essential nutrients for its growth and survival. Burkholderia mallei is aerobically metabolically active, relying on aerobic respiration for energy production. The bacterium utilizes organic compounds as carbon and energy sources, including sugars, amino acids, and fatty acids, which are catabolized through various metabolic pathways such as the tricarboxylic acid (TCA) cycle and glycolysis. Burkholderia mallei possesses nitrogen-fixing capabilities, allowing it to convert atmospheric nitrogen into ammonia through nitrogenase enzymes. This ability enhances its adaptability to nitrogen-limiting environments and contributes to its growth in diverse ecological niches.
The life cycle of Burkholderia mallei involves complex interactions with host cells and the environment, facilitating its replication and spread. Burkholderia mallei infects host cells, primarily epithelial cells and macrophages, through mechanisms such as adhesion, invasion, and intracellular survival. The bacterium employs virulence factors, including adhesins and secretion systems, to establish infection and evade host immune responses. Once inside host cells, Burkholderia mallei establishes intracellular replication niches, where it replicates and proliferates using host cellular machinery and nutrients. The bacterium manipulates host cell signaling pathways and immune responses to create a favorable environment for its survival and propagation. Burkholderia mallei eventually triggers host cell lysis, leading to the release of progeny bacteria into the extracellular environment. The bacterium may also disseminate through cell-to-cell spread or form biofilm communities in host tissues, contributing to chronic infections and disease persistence.
Understanding the cell structure, metabolism, and life cycle of Burkholderia mallei is crucial for elucidating its pathogenic mechanisms and developing targeted interventions for glanders. Insights into the bacterium's metabolic pathways and virulence strategies provide opportunities for the development of novel therapeutics and vaccines to combat infections caused by this medically important pathogen.
Ecology and Pathogenesis
Burkholderia mallei is primarily a pathogen harmful to mammels, with a particular effectiveness for equids like horses, donkeys, and mules. However, it can also infect other species, including humans, dogs, and cats. The bacteria is typically transmitted through direct contact with infected animals or their secretions, respiratory droplets or contaminated body fluids. Human infection with Burkholderia mallei occurs through exposure to infected animals or contaminated environments. Inhalation of bacteria is the most common mode of transmission, leading to the development of glanders. Glanders in humans can manifest as both acute or chronic forms, with symptoms ranging from fever, chills, and respiratory distress to abscess formation in the lungs, lymph nodes, and skin. In severe cases, spread of the infection may lead to septicemia and multi-organ failure thus usually killing the infected person. In animals glanders typically occurs through direct contact with infected equids or ingestion of contaminated food or water. The bacterium can enter the body through mucous membranes, skin abrasions, or inhalation. Clinical signs of glanders in animals include fever, nasal discharge, coughing, and ulcerative lesions in the respiratory tract and skin makes the animals look very clearly ill and deathly. Chronic infection can lead to organ failure, and death if left untreated.
B. mallei has various virulence factors that contribute to its pathogenicity and ability to cause disease in mammalian hosts. The polysaccharide capsule of B. mallei serves asthe key virulence factor, providing protection against host immune defenses and facilitating evasion of phagocytosis. The T6SS of B. mallei is involved in host cell invasion and intracellular survival, allowing the bacterium to manipulate the host cellular processes and establish persistent infections. The LPS molecules on the outer membrane of B. mallei contribute to its pathogenicity by intiating inflammatory responses and modulating host immune signaling pathways.
B. mallei can persist in the environment for extended periods, particularly in soil and water contaminated with infected animal secretions or carcasses. This environment serves as a potential source of infection for susceptible hosts. Changes in environmental conditions, such as increased temperatures and altered precipitation patterns associated with climate change, may influence the distribution and prevalence of B. mallei and other infectious agents. The impact of climate change on glanders epidemiology could warrant further investigation and research.
Overall Understanding the ecology and pathogenesis of B. mallei is essential for implementing effective control measures and mitigating the spread of glanders in both human and animal populations. Strategies for disease prevention and surveillance, including vaccination, biosecurity measures, and early detection of infected individuals and animals, are crucial for minimizing the public health and economic impacts of glanders. Although glanders isn't nearly as prevalent as it once was, understanding how the bacteria functions ecologically could support in research and prevention of other diseases.
References
1.] Godoy, D., Randle, G., Simpson, A. J., Aanensen, D. M., Pitt, T. L., Kinoshita, R., & Spratt, B. G. (2003). Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. Journal of clinical microbiology, 41(5), 2068–2079. https://doi.org/10.1128/JCM.41.5.2068-2079.2003
2.] Song, H., Hwang, J., Yi, H., Ulrich, R. L., Yu, Y., Nierman, W. C., & Kim, H. S. (2010). The early stage of bacterial genome-reductive evolution in the host. PLoS pathogens, 6(5), e1000922. https://doi.org/10.1371/journal.ppat.1000922
3.] Centers for Disease Control and Prevention. (2017, October 31). Glanders. Centers for Disease Control and Prevention. https://www.cdc.gov/glanders/
4.] Lehavi, O., Aizenstien, O., Katz, L. H., & Hourvitz, A. (2002). Harefuah, 141 Spec No, 88–119
5.] Wheelis, M. (n.d.). First shots fired in biological warfare. Nature News. https://www.nature.com/articles/26089
Author
Page authored by Janvi Desai____, student of Prof. Jay Lennon at IndianaUniversity.
